The cytotoxic effect of sunitinib on human bronchial carcinoid cell lines and primary cultures is counteracted by EGF and IGF-1 but not by VEGF

Abstract

Background: Bronchial carcinoids (BC) are rare tumors originating from endocrine cells dispersed in the respiratory epithelium. The main BC treatment is surgery, which is not feasible for large, infiltrating and metastatic disease. In these settings, medical therapy is often tried. Therefore it is important to identify new therapeutic targets and new molecules capable of providing adequate medical treatment for patients with BC. Sunitinib, is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI). Aim: To verify if sunitinib is active in inhibiting cell viability of human BC and what are its targets in these cells. Methods: Human BC cell lines (NCH-727 and NCI-H727 cells) and human BC primary cultures were treated with sunitinib 5 μM and/or EGF 30 nM, IGF1 50 nM, or VEGF 10 nM. Cell viability and caspase 3/7 activation were measured after 48 h of treatment. Results: Sunitinib is capable of inhibiting cell viability of BC cell lines and primary cultures (by 20–50% vs control); moreover sunitinib activates caspase 3/7 (by 20–100% vs control). Both events are counteracted by EGF and IGF-1 at concentrations similar to those found in plasma, but not by VEGF despite its receptors are usually considered the main target of sunitinib. Conclusion: These data indicate that sunitinib is a potential therapeutic agent for treatment of BC, and that its mechanism of action could be mediated, at least in part, by EGFR and IGF1R. Further experiments are needed to deeply understand this issue